U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C31H33F3N2O5S
Molecular Weight 602.6666
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TIPRANAVIR

SMILES

CCC[C@@]1(CCc2ccccc2)CC(=C([C@]([H])(CC)c3cccc(c3)NS(=O)(=O)c4ccc(cn4)C(F)(F)F)C(=O)O1)O

InChI

InChIKey=SUJUHGSWHZTSEU-FYBSXPHGSA-N
InChI=1S/C31H33F3N2O5S/c1-3-16-30(17-15-21-9-6-5-7-10-21)19-26(37)28(29(38)41-30)25(4-2)22-11-8-12-24(18-22)36-42(39,40)27-14-13-23(20-35-27)31(32,33)34/h5-14,18,20,25,36-37H,3-4,15-17,19H2,1-2H3/t25-,30-/m1/s1

HIDE SMILES / InChI

Description
Curator's Comment:: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16802849 | https://www.ncbi.nlm.nih.gov/pubmed/9719600 | http://adisinsight.springer.com/drugs/800008750

Tipranavir (PNU-140690, trade mark APTIVUS) is a potent, orally bioavailable nonpeptidic HIV protease inhibitor of the 5,6-dihydro-4-hydroxy-2-pyrone sulfonamide class. Tipranavir has potent in vitro activity against a variety of HIV-1 laboratory strains and clinical isolates, including those resistant to ritonavir, as well as HIV-2. The drug is launched in several countries, including the US and in the EU. APTIVUS, co-administered with ritonavir, is indicated for combination antiretroviral treatment of HIV-1 infected patients who are treatment-experienced and infected with HIV-1 strains resistant to more than one protease inhibitor.

CNS Activity

Curator's Comment:: Tipranavir do not reach therapeutical concentrations in CSF

Originator

Curator's Comment:: # Pharmacia & Upjohn (now Pfizer)

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
8.0 pM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
APTIVUS

Approved Use

APTIVUS, co-administered with ritonavir, is indicated for combination antiretroviral treatment of HIV-1 infected patients who are treatment-experienced and infected with HIV-1 strains resistant to more than one protease inhibitor (PI). This indication is based on analyses of plasma HIV-1 RNA levels in two controlled studies of APTIVUS/ritonavir of 48 weeks duration in treatment-experienced adults and one open-label 48-week study in pediatric patients age 2 to 18 years. The adult studies were conducted in clinically advanced, 3-class antiretroviral (NRTI, NNRTI, PI) treatment-experienced adults with evidence of HIV-1 replication despite ongoing antiretroviral therapy. The following points should be considered when initiating therapy with APTIVUS/ritonavir: The use of APTIVUS/ritonavir in treatment-naïve patients is not recommended [ see Warnings and Precautions (5.1)

Launch Date

1.1193984E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
77.6 μM
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
TIPRANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FED
94.8 μM
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
TIPRANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: FED
135 μM
375 mg/m² 2 times / day steady-state, oral
dose: 375 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
TIPRANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
710 μM × h
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
TIPRANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FED
851 μM × h
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
TIPRANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: FED
1190 μM × h
375 mg/m² 2 times / day steady-state, oral
dose: 375 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
TIPRANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
6 h
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
TIPRANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FED
5.5 h
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
TIPRANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: FED
8.1 h
375 mg/m² 2 times / day steady-state, oral
dose: 375 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
TIPRANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.1%
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
TIPRANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: FED
Doses

Doses

DosePopulationAdverse events​
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Co-administed with::
ritonavir, oral(200 mg, b.i.d.)
Sources: Page: p.11
unhealthy, 18–65
n = 186
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 18–65
Sex: M+F
Population Size: 186
Sources: Page: p.11
Disc. AE: Gastrointestinal disorder NOS, Gastrointestinal disorder NOS...
AEs leading to
discontinuation/dose reduction:
Gastrointestinal disorder NOS (grade 1, 1%)
Gastrointestinal disorder NOS (moderate, 2.1%)
Gastrointestinal disorder NOS (severe, 1%)
Transaminases increased (grade 1, 1%)
Transaminases increased (moderate, 1.6%)
Transaminases increased (severe, 4.8%)
Sources: Page: p.11
1200 mg 2 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 2 times / day
Sources: Page: p.381
unhealthy, 35.2
n = 10
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 35.2
Sex: M+F
Population Size: 10
Sources: Page: p.381
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Co-administed with::
ritonavir, oral(200 mg, b.i.d.)
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.1
Disc. AE: Hepatitis, Hepatic decompensation...
AEs leading to
discontinuation/dose reduction:
Hepatitis
Hepatic decompensation
Intracranial hemorrhage
Platelet aggregation
Coagulation abnormal
Diabetes mellitus
Hyperglycemia
Immune reconstitution syndrome
Fat redistribution
Lipids increased
Sources: Page: p.1
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Co-administed with::
ritonavir, oral(200 mg, b.i.d.)
Sources: Page: p.1, 5
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.1, 5
Disc. AE: Rash...
AEs leading to
discontinuation/dose reduction:
Rash (0.5%)
Sources: Page: p.1, 5
AEs

AEs

AESignificanceDosePopulation
Gastrointestinal disorder NOS grade 1, 1%
Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Co-administed with::
ritonavir, oral(200 mg, b.i.d.)
Sources: Page: p.11
unhealthy, 18–65
n = 186
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 18–65
Sex: M+F
Population Size: 186
Sources: Page: p.11
Transaminases increased grade 1, 1%
Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Co-administed with::
ritonavir, oral(200 mg, b.i.d.)
Sources: Page: p.11
unhealthy, 18–65
n = 186
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 18–65
Sex: M+F
Population Size: 186
Sources: Page: p.11
Transaminases increased moderate, 1.6%
Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Co-administed with::
ritonavir, oral(200 mg, b.i.d.)
Sources: Page: p.11
unhealthy, 18–65
n = 186
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 18–65
Sex: M+F
Population Size: 186
Sources: Page: p.11
Gastrointestinal disorder NOS moderate, 2.1%
Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Co-administed with::
ritonavir, oral(200 mg, b.i.d.)
Sources: Page: p.11
unhealthy, 18–65
n = 186
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 18–65
Sex: M+F
Population Size: 186
Sources: Page: p.11
Gastrointestinal disorder NOS severe, 1%
Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Co-administed with::
ritonavir, oral(200 mg, b.i.d.)
Sources: Page: p.11
unhealthy, 18–65
n = 186
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 18–65
Sex: M+F
Population Size: 186
Sources: Page: p.11
Transaminases increased severe, 4.8%
Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Co-administed with::
ritonavir, oral(200 mg, b.i.d.)
Sources: Page: p.11
unhealthy, 18–65
n = 186
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 18–65
Sex: M+F
Population Size: 186
Sources: Page: p.11
Coagulation abnormal Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Co-administed with::
ritonavir, oral(200 mg, b.i.d.)
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.1
Diabetes mellitus Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Co-administed with::
ritonavir, oral(200 mg, b.i.d.)
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.1
Fat redistribution Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Co-administed with::
ritonavir, oral(200 mg, b.i.d.)
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.1
Hepatic decompensation Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Co-administed with::
ritonavir, oral(200 mg, b.i.d.)
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.1
Hepatitis Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Co-administed with::
ritonavir, oral(200 mg, b.i.d.)
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.1
Hyperglycemia Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Co-administed with::
ritonavir, oral(200 mg, b.i.d.)
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.1
Immune reconstitution syndrome Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Co-administed with::
ritonavir, oral(200 mg, b.i.d.)
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.1
Intracranial hemorrhage Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Co-administed with::
ritonavir, oral(200 mg, b.i.d.)
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.1
Lipids increased Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Co-administed with::
ritonavir, oral(200 mg, b.i.d.)
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.1
Platelet aggregation Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Co-administed with::
ritonavir, oral(200 mg, b.i.d.)
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.1
Rash 0.5%
Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Co-administed with::
ritonavir, oral(200 mg, b.i.d.)
Sources: Page: p.1, 5
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.1, 5
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
inconclusive
inconclusive
inconclusive
inconclusive
inconclusive
inconclusive
likely
moderate [IC50 16.3 uM]
yes (co-administration study)
Comment: coadministration with dextromethorphan led to potent inhibition of CYP2D5
Page: 100.0
moderate
weak
yes [IC50 0.26 uM]
no (co-administration study)
Comment: coadministration with warfarin had no effect
Page: 100.0
yes [IC50 2.3 uM]
yes [IC50 2.7 uM]
yes [IC50 >50 uM]
yes (co-administration study)
Comment: coadministration with caffeine led to moderate induction at steady state
Page: 100.0
yes
yes
Drug as victim

Drug as victim

Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Antiviral activity of the dihydropyrone PNU-140690, a new nonpeptidic human immunodeficiency virus protease inhibitor.
1997 May
Tipranavir (PNU-140690): a potent, orally bioavailable nonpeptidic HIV protease inhibitor of the 5,6-dihydro-4-hydroxy-2-pyrone sulfonamide class.
1998 Aug 27
6-Hydroxy-1,3-dioxin-4-ones as non-peptidic HIV protease inhibitors.
2000 Dec 4
In vitro antiviral interaction of lopinavir with other protease inhibitors.
2002 Jul
Analysis of protease inhibitor combinations in vitro: activity of lopinavir, amprenavir and tipranavir against HIV type 1 wild-type and drug-resistant isolates.
2004 Mar
Design of HIV-1 protease inhibitors active on multidrug-resistant virus.
2005 Mar 24
Potent inhibition of HIV-1 replication by novel non-peptidyl small molecule inhibitors of protease dimerization.
2007 Sep 28
Novel protease inhibitors (PIs) containing macrocyclic components and 3(R),3a(S),6a(R)-bis-tetrahydrofuranylurethane that are potent against multi-PI-resistant HIV-1 variants in vitro.
2010 Aug
Evaluating the substrate-envelope hypothesis: structural analysis of novel HIV-1 protease inhibitors designed to be robust against drug resistance.
2010 May
Patents

Sample Use Guides

Adults: 500 mg APTIVUS® (tipranavir), co-administered with 200 mg ritonavir, twice daily. Pediatric patients (age 2 to 18 years): Dosing is based on body weight or body surface area not to exceed adult dose.
Route of Administration: Oral
Tipranavir inhibits the replication of laboratory strains of HIV-1 and clinical isolates in acute models of T-cell infection, with EC50 ranging from 0.03 to 0.07 µM (18-42 ng/mL)
Name Type Language
TIPRANAVIR
EMA EPAR   INN   MART.   MI   ORANGE BOOK   VANDF   WHO-DD  
INN  
Official Name English
TIPRANAVIR [WHO-DD]
Common Name English
3'-((1R)-1-((6R)-5,6-DIHYDRO-4-HYDROXY-2-OXO-6-PHENETHYL-6-PROPYL-2H-PYRAN-3-YL)PROPYL)-5-(TRIFLUOROMETHYL)-2-PYRIDINESULFONANILIDE
Systematic Name English
TIPRANAVIR [MART.]
Common Name English
TIPRANAVIR [EMA EPAR]
Common Name English
TIPRANAVIR [ORANGE BOOK]
Common Name English
APTIVUS
Brand Name English
TIPRANAVIR [INN]
Common Name English
TIPRANAVIR [VANDF]
Common Name English
TIPRANAVIR [MI]
Common Name English
Classification Tree Code System Code
NDF-RT N0000000246
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
NCI_THESAURUS C97366
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
EMA ASSESSMENT REPORTS APTIVUS (AUTHORIZED: HIV INFECTIONS)
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
WHO-VATC QJ05AE09
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
LIVERTOX 969
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
WHO-ATC J05AE09
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
NDF-RT N0000175889
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
Code System Code Type Description
RXCUI
190548
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
PRIMARY RxNorm
CAS
174484-41-4
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
PRIMARY
WIKIPEDIA
TIPRANAVIR
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
PRIMARY
PUBCHEM
54682461
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
PRIMARY
MESH
C107201
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
PRIMARY
LACTMED
Tipranavir
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
PRIMARY
FDA UNII
ZZT404XD09
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
PRIMARY
HSDB
8083
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
PRIMARY
MERCK INDEX
M10885
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
PRIMARY Merck Index
ChEMBL
CHEMBL222559
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
PRIMARY
EVMPD
SUB04883MIG
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
PRIMARY
EPA CompTox
174484-41-4
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
PRIMARY
NCI_THESAURUS
C66603
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
PRIMARY
DRUG BANK
DB00932
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
PRIMARY
DRUG CENTRAL
3609
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
PRIMARY
INN
7774
Created by admin on Sat Jun 26 03:02:11 UTC 2021 , Edited by admin on Sat Jun 26 03:02:11 UTC 2021
PRIMARY